title: New treatments for mitochondrial disease-no time to drop our standards.
abstract: Mitochondrial dysfunction is a common cause of inherited multisystem disease that often involves the nervous system. Despite major advances in our understanding of the pathophysiology of mitochondrial diseases, clinical management of these conditions remains largely supportive. Using a systematic approach, we identified 1,039 publications on treatments for mitochondrial diseases, only 35 of which included observations on more than five patients. Reports of a positive outcome on the basis of a biomarker of unproven clinical significance were more common in nonrandomized and nonblinded studies, suggesting a publication bias toward positive but poorly executed studies. Although trial design is improving, there is a critical need to develop new biomarkers of mitochondrial disease. In this Perspectives article, we make recommendations for the design of future treatment trials in mitochondrial diseases. Patients and physicians should no longer rely on potentially biased data, with the associated costs and risks.
authors.affiliation: Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Ageing and Health, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
authors.forename: Gerald
authors.initials: G
authors.lastname: Pfeffer
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
authors.forename: Thomas
authors.initials: T
authors.lastname: Klopstock
authors.forename: Vamsi K
authors.initials: VK
authors.lastname: Mootha
authors.forename: Anu
authors.initials: A
authors.lastname: Suomalainen
authors.forename: Saskia
authors.initials: S
authors.lastname: Koene
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Massimo
authors.initials: M
authors.lastname: Zeviani
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Bindoff
authors.forename: Patrick
authors.initials: P
authors.lastname: Yu-Wai-Man
authors.forename: Michael
authors.initials: M
authors.lastname: Hanna
authors.forename: Valerio
authors.initials: V
authors.lastname: Carelli
authors.forename: Robert
authors.initials: R
authors.lastname: McFarland
authors.forename: Kari
authors.initials: K
authors.lastname: Majamaa
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Turnbull
authors.forename: Jan
authors.initials: J
authors.lastname: Smeitink
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
mesh_terms: D015982:Bias; D006801:Humans; D028361:Mitochondrial Diseases / Q000453:epidemiology / Q000628:therapy*; D015203:Reproducibility of Results